Insight

How Weight is Lost Following Bariatric Surgery Affects the Reversal of Type 2 Diabetes
Stefan Amisten, Senior Medical Writer, Touch Medical Media, UK
Jeremy Betts, Account Director and Advisory Editor, Touch Medical Media, UK
-Insights into STAMPEDE clinical trial from the Cleveland Clinic, presented at AACE, Boston, US, 16–20 May 2018

The increasing incidence of obesity and type 2 diabetes (T2D) is widely recognized as a global epidemic and one of the most challenging contemporary global threats to public health.1

Current T2D treatment goals are aimed at halting disease progression by reducing hyperglycemia, hypertension, dyslipidemia, and other cardiovascular (CV) risk factors,2,3 but fewer than half of diabetes patients manage to achieve and maintain glycemic control through medication alone.4

In observational studies, surgical interventions such as bariatric surgery have been shown to rapidly improve glycemic control and CV risk factors in severely obese T2D patients.5–9 The effects on glycemic control by two types of gastric bypass surgery, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), were recently compared to intensive medical therapy (IMT) in the STAMPEDE clinical trial carried out at the Cleveland Clinic, Cleveland, OH.10,11

Briefly, 150 obese (mean body mass index [BMI] >36) T2D patients were randomized to receive either IMT alone or IMT plus either RYGB or SG. Nine study participants withdrew from the trial, six were lost to follow-up, and one patient died from myocardial infarction at year 4. The remaining 134 study participants completed the 5-year follow-up.10,11 At 5 years, the primary STAMPEDE trial endpoint, reduction in glycated hemoglobin (HbA1c), was met by 5% of patients receiving only IMT, as compared with 29% that were randomized to IMT plus RYGB, and 23% that had IMT plus SG. The proportion of circulating HbA1c in blood is directly correlated to the 3-month average plasma glucose concentration, and is used as a marker for long-term hyperglycaemia and diabetes.12 Study participants that were treated with IMT plus either RYGB or SG had a significantly greater mean percentage HbA1c reduction from baseline than did patients who received IMT alone (2.1% versus 0.3%, p=0.003).11

At the 27th American Association of Clinical Endocrinologists (AACE) meeting, which was held in Boston, MA, on May 16–20, 2018, Dr Keren Zhou, MD, of the Cleveland Clinic Foundation, presented a study on how the rate and duration of weight loss impacts long-term T2D improvement in obese individuals post gastric bypass surgery.

Dr Zhou’s team analyzed the rate of initial weight loss and subsequent weight regain following either RYGB or SG bariatric surgery using 5-year follow-up data of 96 T2D patients that had been randomized to either RYGB or SG bariatric surgery in the STAMPEDE study, and compared the baseline T2D duration and the change in body weight post-surgery with mean HbA1c levels at the 5-year follow-up. At baseline, the study population had a mean age of 48 years, mean BMI of 36.5 kg/m2, mean HbA1c 9.4% and was 66% female.

“In patients that had undergone RYGB, less weight loss in the first year was positively correlated with higher HbA1c at 5 years, whereas in patients that had undergone SG, greater weight regain from the lowest weight post-surgery was positively correlated with higher HbA1c” said Dr Zhou. “Duration of T2D prior to surgery was positively correlated with higher HbA1c in the RYGB cohort, but in the SG cohort, those who lost more weight in the first year had a longer duration of T2D as opposed to those who lost less weight in the first year.”

“This is the first study to investigate the impact of acute and chronic weight changes on T2D improvement following bariatric surgery, and our results suggest that acute weight loss is more important for T2D improvements in RYGB treated patients whereas chronic maintenance of weight loss is more important in patients treated with SG. However, it is possible that the effect of acute weight loss in the SG cohort was obscured as individuals with more weight loss in the SG cohort had a longer duration of T2D and therefore also had a more treatment-resistant T2D at baseline.”

Dr Zhou’s team’s innovative use of 5-year data for the STAMPEDE clinical trial shows that different rates of weight loss impacts T2D differently in obese T2D patients subjected to either RYGB or SG, as improvement in T2D is most strongly correlated with first-year weight loss in the RYGB cohort and that a chronic trajectory of weight loss seems to be more important for SG treated patients.

Although the STAMPEDE trial and other studies have presented convincing evidence of beneficial effects of bariatric surgery in obese T2D patients, further research is needed to determine the long-term efficacy and safety of bariatric surgery, determinants of T2D remission and the effects of combined surgical and pharmacological interventions on obesity and T2D. Further randomized controlled trials with T2D-related hard endpoints are needed to generate robust data to firmly establish bariatric surgery as a staple treatment for obese T2D patients, as a disappointingly low number of patients currently receive surgery.

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